This research proposes to achieve two important goals. (1) To further our understanding of the natural history of multiple sclerosis by utilizing magnetic resonance imaging in conjunction with volumetric and individual lesion quantitation. Only with quantitative techniques can longitudinal imaging data be meaningfully compared. Such quantitative techniques presently offer an accurate method of assessing not only changes in individual lesions but also brain parenchymal and cerebrospinal fluid volume, total lesion volume (high intensity abnormalities on long TR images), and the volume of active disease (gadopentetate dimeglumine [Gd] enhanced lesion volume). This study will answer a basic but unresolved question concerning the extent to which individual MS lesions and volumes as well as activity change over a 5 year duration. We will also relate this data to clinical status. The correlation of the clinical features of MS with quantitative assessment of enhancing and unenhancing lesions in a prospective study has never been performed. Physicians have an important responsibility to counsel patients and their families concerning prognosis in MS, yet there is presently only superficial descriptive information regarding the natural history of MR demonstrated MS lesions. Quantitative MR imaging will also resolve whether MS activity occurs in waves with some lesions then progressing and others regressing or whether there is random activity i.e. individual lesions come and go independently. This data is essential in order to design and assess treatment regimens. (2) The other major thrust of the proposal is application of localized 1H spectroscopy to analyze selected MS lesions and to further characterize them into lesions which are demyelinating (possessing IH spectra with myelin catabolites) and those that are edematous or gliotic (without 1H spectral evidence of myelin catabolites). We will then follow, using localized 1H spectroscopy, certain enhancing and unenhancing lesions over the study's duration. Gd enhancement will separate active from inactive lesions while localized 1H spectroscopy will further divide the lesions based upon their 1H spectroscopic properties. Subpopulations of lesions will thus be identified and these groups may have similar natural histories. Individual lesion, volumetric and 1H spectroscopic longitudinal data in combination with Gd enhanced imaging will: (a) provide new insights into the natural history of MS; (b) generate a method to characterize individual lesions and assess outcome of both individual plaques and aggregate disease; (c) possibly allow diagnosis of definite MS based upon imaging and spectroscopic results (identify old and new lesions at one time); (d) produce an accurate new classification scheme of MS based imaging and spectroscopic data; and (d) perhaps serve as both a foundation for therapeutic interventions as well as a marker to assess effectiveness of proposed MS therapies.